2/16/2011 International Research: Applying Ethical Principles and - PDF document

2/16/2011 International Research: Applying Ethical Principles and Research Guidelines in Global Settings February 16, 2011 1:00-2:30 PM ET Welcome International Research: Applying Ethical Principles and Research Guidelines in Global Settings A 90-minute Joan Rachlin, JD, MPH interactive webinar Executive Director Nancy Kass, ScD David A. Borasky, Jr., MPH, CIP Phoebe R. Berman Professor IRB Manager Johns Hopkins Bloomberg School of Public Health Office of research protection Deputy Director for Public Health RTI International Berman Institute of Bioethics 1

2/16/2011 Issues to Consider for IRBs that Review International Research Involving Vulnerable Populations David A. Borasky, Jr., MPH, CIP Office of Research Protections RTI International Overview  FWA Considerations  Regulatory expectations for IRBs  Scenarios where regulations are difficult to export What does your FWA say?  If a U.S. institution: • Ethical standards = Belmont • Procedural standards = Common Rule  What if a non-US institution? 2

2/16/2011 Is there really a choice? Federal Register Notice ―Interpretation of Assurance Requirements‖ “ Some regulated institutions may have been confused by the fact that several … procedural standards are listed on the FWA form for … non- U.S. institutions…” (FR: July 7, 2006 Volume 71, Number 130) Interpretation of Assurance Requirements “…and interpreted this to mean that non -U.S. institutions have a choice of whether or not the requirements of 45 CFR part 46 must be met for HHS conducted or -supported research conducted at their institutions.” “Such an interpretation would be erroneous.” (FR: July 7, 2006 Volume 71, Number 130) 3

2/16/2011 Interpretation of Assurance Requirements “For HHS -conducted or -supported research, all institutions holding an … FWA … must comply with the requirements of 45 CFR part 46. That compliance is required regardless of whether the institution marked … other procedural standards on the FWA form… .” (FR: July 7, 2006 Volume 71, Number 130) Why is this a problem?  The local IRB may not have made required regulatory determinations  IRB roster may not include members required by Common Rule  Continuing review may not occur with frequency required by Common Rule  Protections for special populations may not contain specific sub-part requirements When relying on a local IRB  Communicate with local IRBs  Determine what standards were applied in review of research – ask specific questions  Be clear in IRB records what portion of local review you are relying on  Maintain complete documentation 4

2/16/2011 Expectations for IRBs from the Belmont Report and the Common Rule when Reviewing Research on Vulnerable Populations Belmont When vulnerable populations are involved in research, the appropriateness of involving them should itself be demonstrated. A number of variables go into such judgments, including the nature and degree of risk, the condition of the particular population involved, and the nature and level of the anticipated benefits. Approval Criteria (45 CFR 45.111(a)(3)) Selection of subjects is equitable…. the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be should be particularly cognizant of the special problems of research involving vulnerable populations …. 5

2/16/2011 IRB Membership (45 CFR 46.107(a)) If an IRB regularly reviews research that involves a vulnerable category of subjects, such as …. consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects. Meeting Expectations  Identify an expert with relevant background and experience • PRIM&R International Members • Fogarty-supported Bioethics Program Trainees  Obtain an opinion from an experienced member of the site IRB  Require site IRB approval first Meeting Expectations  Create a supplement to your IRB application • Design the questions to address issues commonly raised by the IRB  Require PI participation in IRB meetings  Require more rigorous/frequent monitoring 6

2/16/2011 Other Resources  NBAC report on international research  CIOMS and other international guidelines  OHRP’s International Activities Program  FIC International Research Ethics Resources  NGOs that work with the population/in region Common Scenarios that Challenge US IRBs when Reviewing International Research Informed Consent  International application of Western informed consent standards • Different beliefs about autonomy o Role of elders / community leaders / head of household • Translation issues • Documentation issues o Mistrust of signing papers o Illiteracy 7

2/16/2011 Research with Children  Research with Minors • Local definitions of minor; guardian • Parental permission requirements • Research with orphans and vulnerable children  Identify the issues in advance and proactively address them. Document findings! Local Laws  Absence of regulation / policy regarding research (and limited or no enforcement)  Common practice versus legal requirements in the provision of healthcare  Multi-national research = multiple local norms Maintain Appropriate Documentation  Credible sources – official email / letterhead  Joe_PI@yahoo.com may not be best resource!  Written correspondence rather than verbal assurance  If in doubt, seek second opinion / obtain additional confirmation  Maintain good documentation 8

2/16/2011 Toward valid and respectful Informed Consent in Resource Poor Countries Nancy Kass, ScD Berman Institute of Bioethics and Bloomberg School of Public Health Johns Hopkins University Assumptions  Experienced audience  Familiar with informed consent generally  Interested in how experience with informed consent can be applied internationally Elements of informed consent  Disclosure of Information  Understanding  Voluntary Authorization  Competence 9

2/16/2011 Disclosure – additional considerations  Think more broadly about when, how, to whom to disclose • Community or group introduction of study (first) o Street theater o Radio announcements o Group discussions o Community liaisons o Involvement of family members/others • Individual disclosure and discussion (later) o More pictures and props Disclosure – additional considerations  Background work (Rapid Ethnographic Assessment) • Helps identify the best strategies for target population • Helps ensure messages are appropriate, clear, sensible to target audiences Understanding – additional considerations  May be limited familiarity with research • Doctor admitting uncertainty is problematic  Usual procedures may be misunderstood • Blood drawing • Signing of forms • ―We fill in the narratives we don’t understand‖ 10

2/16/2011 Understanding – additional considerations  No word for ―research‖ or ―placebo‖ or ―privacy‖ • Explanations can be lengthy • Explanations can be inaccurate!!  No standards re: translation quality (back translation helps) Assessing understanding becomes important  Most investigators do not assess understanding (Tomamichel 1995; Kass 2005) • 65% investigators thought assessing understanding was important • 16% of them did so Helpful strategies Ethnographic work to guide and improve disclosure When, how, to whom Wording, analogies that make sense Emphasize key concepts (?) What are 5 most important things to understand? Explain WHY key procedures are done (not just HOW) Assessment of understanding Quizzes pretty good (―corrected feedback‖) Best (?) may be verbalization of key concepts (simple!!) Community discussions DURING project also 11

2/16/2011 Project staff (in country) comments about enrollment/voluntariness ―What if we really believe it is the best thing for them to be in the study?‖ ―If we don’t enroll enough people the study/we will be in trouble.‖ ―If she changes her mind, you try to convince her otherwise.‖ Informed Consent- Concluding messages Ethnographic work : beliefs about disease, about research, how concepts are described ― Menu of methods ‖ for informing Listen to local people — their ideas re: informing, communicating, checking understanding Question/answer to check understanding What is most important? Certain aspects of research will be misunderstood: try to anticipate and be creative; determine which are essential Informed consent: concluding messages Respect both/multiple traditions for informing and decision-making, if possible Training for ― on the ground ‖ staff essential Informed consent is ―necessary but not sufficient‖ for an ethical study; participants still expect (and deserve) protection Think beyond the consent form!!! 12

2/16/2011 Considering Beneficence in International Research David A. Borasky, Jr., MPH, CIP Office of Research Protections RTI International Beneficence  Minimizing risk of harm • individual vs group harms • physical/psychological vs social harms  Maximizing benefits • individual vs community • extent of researchers obligations Minimizing risk  Individual level harms • physical/psychological • social harms  Group/community level harm • what are the research associated risks? • are there measures to minimize risk? 13